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B R I E F R E P O R T
High Prevalence of Anorectal
Chlamydial Infection in HIV-Infected
Men Who Have Sex with Men
in Switzerland
Thanh Dang,1Katia Jaton-Ogay,2Markus Flepp,3Helen Kovari,4
John-Marc Evison,5Jan Fehr,6Patrick Schmid,7
Emmanuelle Boffi El Amari,8Matthias Cavassini,1Massimo Odorico,9
Philip E. Tarr,10Gilbert Greub,1,2and the Swiss HIV Cohort Study
1Infectious Diseases Service, University Hospital Center, and2Institute
of Microbiology, University of Lausanne and University Hospital Center, Lausanne,
3Center for Infectious Diseases, Klinik im Park, and4Division of Infectious
Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich,
5Department of Infectious Diseases, University Hospital Bern, Bern,6Division
of Infectious Diseases, University Hospital Basel, Basel,7Infectious Disease Unit,
Hospital St-Gall, St-Gall,8HIV-AIDS Unit and Infectious Disease Consultations,
University Hospital Geneva, Geneva,9Infectious Disease Service, Hospital
Lugano, Lugano, and10Infectious Diseases Service, Kantonsspital Bruderholz,
University of Basel, Bruderholz, Switzerland
Human immunodeficiency virus (HIV)–infected men who have sex with men (MSM) were enrolled in an anorectal Chlamydia trachomatis screening study. Anorectal Chlamy-dia DNA was detected in 16 (10.9%) of 147 men, mainly among asymptomatic patients and patients having120 sexual
partners. These results support routine anorectal Chlamydia screening in HIV-infected MSM who report unprotected anal intercourse.
In several Western countries, including Switzerland, an increas-ing proportion of new human immunodeficiency virus (HIV) infection is occurring in men who have sex with men (MSM). Concomitantly, several European countries have recorded a re-cent, substantial increase in the number of reported sexual-ly transmitted diseases (STDs), particularsexual-ly among MSM [1]. STDs, including nonulcerative, frequently asymptomatic infec-tions such as Chlamydia trachomatis infection, are associated with a several-fold increased likelihood of acquiring HIV in-fection [2, 3]. Anorectal chlamydial inin-fection might thus be a
Received 11 June 2009; accepted 1 July 2009; electronically published 22 October 2009. Reprints or correspondence: Dr Philip Tarr and Dr Gilbert Greub, Infectious Diseases Service and Institute of Microbiology, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland (philip.tarr@unibas.ch and gilbert.greub@chuv.ch).
Clinical Infectious Diseases 2009; 49:1532–5
2009 by the Infectious Diseases Society of America. All rights reserved. 1058-4838/2009/4910-0012$15.00
DOI: 10.1086/644740
contributor to the uncontrolled HIV epidemic among MSM. The aim of this study was to determine the prevalence and clinical characteristics of anorectal chlamydial infection in HIV-infected MSM who were followed up in the Swiss HIV Cohort Study (SHCS) [4] and to evaluate the feasibility of anorectal STD screening in routine HIV care.
Methods. Participants were enrolled in the SHCS, which involves a standardized follow-up visit every 6 months that includes questions about sexual activity and condom use [5]. From 1 April 2007 through 31 March 2008, consecutive MSM participants who reported⭓1 episode of unprotected receptive anal intercourse in the previous 2 years and/or symptoms of proctitis (rectal pain and/or discharge, cramps, bloody stools, or new onset and/or unusual constipation) were invited to be tested for anorectal chlamydial infection. All participants gave written, informed consent, and the study was approved by the ethics committees of participating SHCS centers.
A standardized questionnaire was used to record the follow-ing: (1) sexual behavior (including use of sex toys, fisting, oro-anal contact, and trading sex for money), (2) number of sex partners within the previous 2 years, (3) knowledge of partner’s HIV serostatus, (4) history of STD, and (5) anorectal, urogen-ital, or systemic symptoms at the time of the visit. Data on demographic characteristics, CD4 cell count, HIV viral load, current antiretroviral therapy, syphilis, hepatitis B virus infec-tion, and hepatitis C virus infection were retrieved from the SHCS database. Study physicians were provided with kits that contained the questionnaire, a sterile dry cotton-tipped swab (Eurotubo; Deltalab), a sterile tube containing 500 ml of DNA-free water, and detailed instructions. Specimens were obtained by the treating physician by passing the swab 3–4 cm into the anal canal and by rubbing the swab against the anal wall with a rotating motion for 30 seconds. Anorectal cells were exudated from the swab by pressing the swab inside the DNA-free water tube.
All specimens were processed at the Institute of Microbiology in Lausanne. Samples were screened for the presence of C. trachomatis DNA by means of a TaqMan real-time polymerase chain reaction (PCR) assay that targeted the cryptic plasmid of C. trachomatis, as described elsewhere [6]. This validated assay also detects strains that contain a recently identified 350 bp deletion in the cryptic plasmid [7], because the 71 bp DNA fragment amplified is located 93 bp downstream from the de-letion. Positive samples were genotyped by partial amplification and sequencing of the C. trachomatis ompA gene fragments, as described elsewhere [8]. Obtained sequences were compared
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Table 1. Risk Factors Associated with Anorectal Chlamydia trachomatis Infection among 147 Male Homosexual Participants in the
Swiss HIV Cohort Study
Variable With anorectal C. trachomatis infection (n p 16) Without anorectal C. trachomatis infection (n p 131) OR (95% CI), by univariate analysis P
Medical history and clinical characteristics
Age, median years (IQR) 39.5 (32–47) 42 (27–65) 0.75 (0.39–1.41)a .39
Median CD4 cell count 529 cells/mL 459 cells/mL 0.35 (0.03–3.59)b .37b
HIV-1 RNA!40 copies/mL 11 (69) 77 (59) 0.36 (0.21–1.97) .44
Current combination antiretroviral therapy 13 (81) 93 (71) 1.77 (0.47–6.56) .55
Drug usec 5 (31) 38 (29) 1.11 (0.36–3.41) .85
Alcohol misused 5 (31) 51 (39) 0.71 (0.23–2.17) .59
Hepatitis C seropositivity 2 (13) 10 (8) 1.83 (0.36–9.27) .36
Chronic hepatitis B infection 0 (0) 9 (7) .59
Concurrent proctitis symptoms 3 (19) 25 (19) 0.97 (0.25–3.69) 1.99
Concurrent urogenital symptoms 1 (6) 12 (9) 0.66 (0.08–5.45) 1.99
History of STDs 11 (69) 88 (67) 1.07 (0.35–3.28) .89
Chlamydial infection 4 (25) 31 (24) 1.07 (0.32–3.57) 1.99
Gonorrhea 5 (31) 58 (44) 0.57 (0.18–1.73) .32
Syphilise 9 (56) 55 (42) 1.77 (0.62–5.06) .28
Sexual behavior and practices within previous 2 years
Median no. of partners (IQR) 22 (10–100) 6 (2–13) 1.01 (1–1.02)f .002
120 sex partners 8 (50) 17 (13) 5.64 (1.86–17.09) .001
Intercourse with HIV-infected partner(s) or declines to answer 14 (88) 92 (70) 2.96 (0.64–13.67) .23 Consistent condom use with occasional partnerg 8 (50) 51 (39) 0.63 (0.22–1.80) .39
Any anal insertive sex 11 (69) 79 (60) 1.44 (0.47–4.40) .51
Any oral insertive sex 13 (81) 84 (64) 2.42 (0.65–8.94) .26
Any vaginal insertive sex 1 (6) 4 (3) 2.11 (0.22–20.19) .44
Any oral receptive sex 14 (88) 102 (78) 1.99 (0.42–9.26) .52
Being fisted 1 (6) 15 (11) 0.51 (0.06–4.18) 1.99
Use of anal toys 7 (44) 33 (25) 2.30 (0.79–6.69) .12
Oro-anal contact 9 (56) 71 (54) 1.08 (0.38–3.09) .88
Ever exchanged money for sex 1 (6) 14 (11) 0.55 (0.06–4.54) 1.99
NOTE. Values shown are no. (%) of patients, unless otherwise indicated. CI, confidence interval; HIV, human immunodeficiency virus; IQR, interquartile range; OR, odds ratio; STD, sexually transmitted disease.
a
Per 10-year increase in age. b !
200 cells/mL vs⭓200 cells/mL. c
Injection or noninjection drug use within the previous 6 months. d
Daily consumption of⭓30 g alcohol. e
Positive serum Treponema pallidum hemagglutination assay. f
Per 1 sex partner increase, within the previous 2 years. g
Always used condoms with occasional partners during the previous 6 months.
with Chlamydia GenBank sequences for serovar identification. In addition, the presence of Neisseria gonorrhoeae DNA was investigated in all specimens by means of a specific homemade TaqMan PCR assay that targeted the 5region of the porA gene with the following primers and probes: NgF 5CGAAGTCAA
AGCTGGTGTGG, NgR 5 TAACTGTATTGCCCGTTTGAC
CTT, and NgS 5VIC CAGTTGACCGAGCCAC– MGB at con-centrations of 200 nmol (primers) and 100 nmol (probe). This homemade PCR assay exhibits an excellent specificity, as shown by the fact that no amplification was detected when testing 10 ng of DNA extracted from various bacterial species: Neisseria
lactamica, Neisseria meningitidis, Neisseria subflava, Neisseria wea-veri, Enterococcus faecalis, Escherichia coli, Pseudomonas aerugi-nosa, Staphylococcus species, and Streptococcus pyogenes.
Demographic data and risk factors were compared between patients with and patients without C. trachomatis infection by the Pearson x2 test (or the Fisher exact test when indicated) for categorical variables. For continuous variables, medians were compared by the Wilcoxon-Mann-Whitney test. Multi-variate logistic regression was performed to identify factors in-dependently associated with C. trachomatis infection. All anal-yses were performed using Stata, version 10 (StataCorp).
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Results. Very few patients declined to be screened, and the anorectal swabbing procedure was found to be acceptable and minimally discomforting by all study participants. Of 157 spec-imens received in the laboratory, 10 were rejected because of either protocol violation (n p 6), missing questionnaire (n p ), or noninterpretable result due to presence of PCR inhibi-2
tors (n p 2). The final analysis thus included 147 anal speci-mens obtained from 147 participants, with the following char-acteristics: white race, 93%; median age, 42 years (range, 22– 72 years); at least high-school education, 93%; median CD4 cell count, 459 cells/mL (interquartile range, 332–676 cells/mL); receipt of antiretroviral therapy, 72%; HIV-1 RNA!40 copies/
mL, 60%; illicit or recreational drug use, 29%; and history of STD, 67% (Table 1).
Anorectal C. trachomatis DNA was detected in 16 (10.9%) of the 147 specimens (95% confidence interval [CI], 6.2%– 17.6%) and N. gonorrhoeae DNA in 4 (2.7%; 95% CI, 0.9%– 7.3%). No participant had concomitant C. trachomatis and N. gonorrhoeae infection. There was 1 lymphogranuloma vene-reum (LGV) serovar. The non-LGV serovars included G (n p ), J ( ), E ( ), and D ( ). Serovars could not be
5 n p 4 n p 2 n p 1
determined in 3 samples because of very low bacterial loads (threshold cycles between 37 and 40.4). Current proctitis symp-toms were reported by 28 participants; infection with C. tra-chomatis was found in 3 participants, and N. gonorrhoeae was found in 1 of these. The participant with anorectal LGV had a 7-day history of rectal discharge, cramps, and bloody stools. He had a history of C. trachomatis proctitis and syphilis and report-ed160 partners during the previous 2 years.
Table 1 shows the characteristics of patients with (n p 16) and those without (n p 131) anorectal chlamydial infection. Proctitis symptoms were not associated with chlamydial infec-tion. Having120 sex partners within the previous 2 years was
reported by 8 (50%) of the 16 participants with chlamydial in-fection, compared with 17 (13%) of the 131 participants without chlamydial infection. In a model adjusted for age (per 10 years), insertive anal intercourse, and inconsistent condom use, the odds ratio of anorectal C. trachomatis infection was 5.52 (95% CI, 1.78–17.11) for participants with120 partners within the
pre-vious 2 years. There was a trend (P p .12) toward anal toy use being associated with anorectal chlamydial infection.
Discussion. The main finding of our study is a high prev-alence of anorectal C. trachomatis infection among HIV-in-fected MSM in Switzerland who report unprotected sexual ac-tivity, most of whom presented for routine HIV care. The high prevalence together with a strong association with multiple sex partners and their presumed potential for facilitating HIV transmission suggest a possible role for anorectal chlamydial infection in sustaining the ongoing HIV epidemic among MSM in Switzerland. Consistent with prior reports [9], most ano-rectal chlamydial infections were asymptomatic, indicating the
need for increased awareness of these infections among HIV-infected MSM. Our findings underscore a potential role for expanded rectal chlamydial screening in the reduction of the number of new HIV infections among MSM, a group for whom increased HIV prevention efforts are particularly needed. Early detection and treatment of curable STDs was already recom-mended in a 1998 report by the United States Centers for Disease Control and Prevention (CDC) that also highlighted the importance of asymptomatic infection [3]. Moreover, the CDC recommends at least annual screening for rectal STDs in MSM who report receptive anal intercourse [10].
Our findings are consistent with the high rectal chlamydial infection rate among MSM with newly diagnosed HIV infection in San Francisco [11] and may be related to increased sexual risk-taking behavior among MSM in the era of antiretroviral therapy. In contrast, only one participant had LGV, consistent with the low rectal LGV rate in patients at STD clinics in the United Kingdom [12]. This argues against anorectal LGV be-ing a major driver of the recent doublbe-ing of the number of new HIV infections among MSM in Switzerland.
In our data set, the only risk factor for anorectal chlamydial infection was the number of sex partners in the previous 2 years. Detection of additional associations with specific sexual practices presumably was limited by the fact that participants were selected for unprotected anal intercourse, a marker for high-risk sexual activity.
In contrast to previous studies that investigated anorectal chlamydial infection among patients at STD clinics [12, 13], most participants in our study presented for routine HIV care to SHCS-affiliated physicians and were consecutively enrolled on the basis of a single, simple screening question (unprotected anal intercourse in the previous 2 years). We therefore believe that our data represent the current epidemiology of anorectal chlamydial infection in a population representative of sexually active HIV-infected MSM in Switzerland. In conclusion, regular anorectal chlamydial screening should be strongly considered in all HIV-infected MSM who report unprotected anal inter-course, irrespective of symptoms. Additional studies should ad-dress the incidence of other anorectal STDs in high-risk HIV-infected MSM, the appropriate frequency of screening, and the indication to screen for other STDs in this setting.
Members of the Swiss HIV Cohort Study. M. Battegay, E. Bernasconi, J. Bo¨ni, H. C. Bucher, P. Bu¨rgisser, A. Calmy, S. Cattacin, M. Cavassini, R. Dubs, M. Egger, L. Elzi, M. Fischer, M. Flepp, A. Fontana, P. Francioli (president of the SHCS), H. Furrer (chairman of the Clinical and Laboratory Committee), C. Fux, M. Gorgievski, H. Gu¨nthard (chairman of the Scientific Board), H. Hirsch, B. Hirschel, I. Ho¨sli, C. Kahlert, L. Kaiser, U. Karrer, C. Kind, T. Klimkait, B. Ledergerber, G. Martinetti, B. Martinez, N. Mu¨ller, D. Nadal, F. Paccaud, G. Pantaleo, A. Rauch, S. Regenass, M. Rickenbach (head of Data Center), C.
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Rudin (chairman of the Mother and Child Substudy), P. Schmid, D. Schultze, J. Schu¨pbach, R. Speck, P. Taffe´, A. Telenti, A. Trkola, P. Vernazza, R. Weber, and S. Yerly.
Acknowledgments
We thank Franziska Schoni-Affolter, Cyril Andre´, Rene´ Brouillet, and Se´bastien Aeby for their technical help and Ve´ronique Erard for her valuable comments.
Financial support. The Swiss HIV Cohort Study, which is support-ed by the Swiss National Science Foundation; Leenards Foundation (ca-reer award titled Bourse Leenards pour la rele`ve acade´mique en me´decine clinique a` Lausanne, to G.G.).
Potential conflicts of interest. All authors: no conflicts.
References
1. Fenton KA, Lowndes CM. Recent trends in the epidemiology of sex-ually transmitted infections in the European Union. Sex Transm Infect
2004; 80:255–63.
2. Fleming DT, Wasserheit JN. From epidemiological synergy to public health policy and practice: the contribution of other sexually trans-mitted diseases to sexual transmission of HIV infection. Sex Transm Infect 1999; 75:3–17.
3. HIV prevention through early detection and treatment of other sexually transmitted diseases—United States. Recommendations of the Advi-sory Committee for HIV and STD Prevention. MMWR Recomm Rep
1998; 47(RR-12):1–24.
4. Swiss HIV Cohort Study. 2000. Available at: http://www.shcs.ch. Ac-cessed 22 September 2009.
5. Glass TR, Young J, Vernazza PL, et al. Is unsafe sexual behaviour increasing among HIV-infected individuals? AIDS 2004; 18:1707–14. 6. Jaton K, Bille J, Greub G. A novel real-time PCR to detect Chlamydia
trachomatis in first-void urine or genital swabs. J Med Microbiol 2006;
55:1667–74.
7. Ripa T, Nilsson P. A variant of Chlamydia trachomatis with deletion in cryptic plasmid: implications for use of PCR diagnostic tests. Euro Surveill 2006; 11:E061109.2.
8. Pedersen LN, Kjaer HO, Moller JK, Orntoft TF, Ostergaard L. High-resolution genotyping of Chlamydia trachomatis from recurrent uro-genital infections. J Clin Microbiol 2000; 38:3068–71.
9. Kent CK, Chaw JK, Wong W, et al. Prevalence of rectal, urethral, and pharyngeal chlamydia and gonorrhea detected in 2 clinical settings among men who have sex with men: San Francisco, California, 2003. Clin Infect Dis 2005; 41:67–74.
10. Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep 2006; 55:1–94.
11. Scott KC, Philip S, Ahrens K, Kent CK, Klausner JD. High prevalence of gonococcal and chlamydial infection in men who have sex with men with newly diagnosed HIV infection: an opportunity for same-day pre-sumptive treatment. J Acquir Immune Defic Syndr 2008; 48:109–12. 12. Ward H, Alexander S, Carder C, et al. The prevalence of
lympho-granuloma venereum (LGV) infection in men who have sex with men: results of a multicentre case finding study. Sex Transm Infect 2009; 85:173–5.
13. Van der Bij AK, Spaargaren J, Morre SA, et al. Diagnostic and clinical implications of anorectal lymphogranuloma venereum in men who have sex with men: a retrospective case-control study. Clin Infect Dis
